Our group has identified reduced sleep duration and reduced sleep quality as novel risk factors for type 2 diabetes. Type 2 diabetes develops when the pancreatic beta cells fail to release enough insulin to compensate for the degree of insulin resistance of peripheral tissues. Reductions in sleep duration or in sleep quality both result in increased insulin resistance without appropriate compensation by beta cell release. We have further obtained evidence indicating that beta cell function in young healthy adults is strongly correlated with baseline levels of slow-wave activity (SWA; EEG spectral power in the 0.5-4 Hz range), the primary marker of sleep-wake homeostasis. Studies completed during the previous grant period have, however, shown that during repeated partial sleep deprivation, SWA does not increase despite the increased cumulated duration of wakefulness. This allostasis of SWA with recurrent sleep loss could accelerate age-related declines in the homeostatic control of sleep. SWA decreases markedly with age and sex differences have been well-recognized. We have recently identified robust ethnic differences in SWA, with African-Americans having lower levels of SWA than whites. SWA is a remarkably stable trait-dependent characteristic that varies greatly from one individual to another. Heritability of SWA has not yet been evaluated. The overall goal of this project is to test the hypothesis that individuals with low SWA, because of age, ethnicity, sex or genetic factors, are more susceptible to develop type 2 diabetes because they have reduced beta cell function and, therefore a higher vulnerability to the metabolic challenge of sleep disturbances. To achieve this goal, we will combine statistical analyses of the very large data base accumulated from studies conducted by our group during the past 10 years, with a direct experimental approach and an exploration of genetic factors that could underlie both the regulation of SWA and genetic susceptibility to diabetes. The findings from this project are expected to demonstrate the importance of preserving or improving sleep quality to reduce the risk of type 2 diabetes. RELEVANCE (See instructions): The incidence of type 2 diabetes is increasing in the U.S. and worldwide. This project will determine the role of reductions in sleep duration and quality in the risk of type 2 diabetes. The findings could lead to novel strategies to delay the development or reduce the severity of type 2 diabetes.